DESCRIPTION: The importance of better understanding the retroviral replication cycle in order to identify novel targets for viral control is imperative. The avian retrovirus Rous sarcoma virus (RSV), the first virus linked to cancer, remains the prototype oncoretrovirus. This proposal focuses on the role of one of the major RSV structural protein, the Gag matrix (MA) protein, in viral infection. Little is known about the events leading to viral integration, a key step in replication. Work from the applicant s laboratory suggests that the RSV MA protein may play a key, undescribed, role in integration. Several mutants within MA were identified that led to efficient production of noninfectious particles. In one class of mutants, there was a late bock to infection, most likely occurring immediately before integration. The first specific aim is to examine whether MA is involved in integration. A second class of mutants resulted in an infectivity block much earlier in infection, prior to the initiation of reverse transcription. The second specific aim addresses the hypothesis that MA also functions during receptor binding and fusion. The third specific aim will characterize new MA mutants which will be created using information from the MA structure and conserved motifs. The fourth aim will examine how the virus interfaces with the cell during infection and seeks to identify viral and cellular partners of MA during early stages of infection. All of these studies are centered on the activity of a single protein during an important part of the retroviral life cycle.